排序方式: 共有237条查询结果,搜索用时 15 毫秒
111.
Chavarría M Santiago C Platero R Krell T Casasnovas JM de Lorenzo V 《The Journal of biological chemistry》2011,286(11):9351-9359
The catabolite repressor/activator (Cra) protein is a global sensor and regulator of carbon fluxes through the central metabolic pathways of Gram-negative bacteria. To examine the nature of the effector (or effectors) that signal such fluxes to the protein of Pseudomonas putida, the Cra factor of this soil microorganism has been purified and characterized and its three-dimensional structure determined. Analytical ultracentrifugation, gel filtration, and mobility shift assays showed that the effector-free Cra is a dimer that binds an operator DNA sequence in the promoter region of the fruBKA cluster. Furthermore, fructose 1-phosphate (F1P) was found to most efficiently dissociate the Cra-DNA complex. Thermodynamic parameters of the F1P-Cra-DNA interaction calculated by isothermal titration calorimetry revealed that the factor associates tightly to the DNA sequence 5′-TTAAACGTTTCA-3′ (KD = 26.3 ± 3.1 nm) and that F1P binds the protein with an apparent stoichiometry of 1.06 ± 0.06 molecules per Cra monomer and a KD of 209 ± 20 nm. Other possible effectors, like fructose 1,6-bisphosphate, did not display a significant affinity for the regulator under the assay conditions. Moreover, the structure of Cra and its co-crystal with F1P at a 2-Å resolution revealed that F1P fits optimally the geometry of the effector pocket. Our results thus single out F1P as the preferred metabolic effector of the Cra protein of P. putida. 相似文献
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Fredriksson AG Zajac J Eriksson J Dyverfeldt P Bolger AF Ebbers T Carlhäll CJ 《American journal of physiology. Heart and circulatory physiology》2011,301(6):H2344-H2350
Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 ± 0.3 mJ) than the other flow components (P < 0.001 and P < 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P < 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology. 相似文献
113.
Albert Mayola Oihane Irazoki Ignacio A. Martínez Dmitri Petrov Filippo Menolascina Roman Stocker José A. Reyes-Darias Tino Krell Jordi Barbé Susana Campoy 《PloS one》2014,9(8)
The RecA protein is the main bacterial recombinase and the activator of the SOS system. In Escherichia coli and Salmonella enterica sv. Typhimurium, RecA is also essential for swarming, a flagellar-driven surface translocation mechanism widespread among bacteria. In this work, the direct interaction between RecA and the CheW coupling protein was confirmed, and the motility and chemotactic phenotype of a S. Typhimurium ΔrecA mutant was characterized through microfluidics, optical trapping, and quantitative capillary assays. The results demonstrate the tight association of RecA with the chemotaxis pathway and also its involvement in polar chemoreceptor cluster formation. RecA is therefore necessary for standard flagellar rotation switching, implying its essential role not only in swarming motility but also in the normal chemotactic response of S. Typhimurium. 相似文献
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Hongcai Li Chao Wang Tino Sanchez Yanmei Tan Chunying Jiang Nouri Neamati Guisen Zhao 《Bioorganic & medicinal chemistry》2009,17(7):2913-2919
HIV-1 integrase, which catalyzes the integration of the viral genome into the cellular chromosome, is an essential enzyme for retroviral replication, and represents an attractive and validated target in the development of therapeutics against AIDS. In this paper, 17 amide-containing novel diketoacids were designed and synthesized, and their ability to inhibit HIV-1 integrase was tested. The structure–activity relationships were also analyzed. 相似文献
118.
Brettschneider J Mogel H Lehmensiek V Ahlert T Süssmuth S Ludolph AC Tumani H 《Neurochemical research》2008,33(11):2358-2363
Cerebrospinal fluid (CSF) is a promising source of biomarkers in amyotrophic lateral sclerosis (ALS). Using the two-dimensional
difference in gel electrophoresis (2-D-DIGE), we compared CSF samples from patients with ALS (n = 14) with those from normal controls (n = 14). Protein spots that showed significant differences between patients and controls were selected for further analysis
by MALDI-TOF mass spectrometry. For validation of identified spots western blot analysis and ELISA was performed. We identified
2 proteins that were upregulated and 3 proteins that were down-regulated in CSF in ALS. Of these, two proteins (Zn-alpha-2-glycoprotein
and ceruloplasmin precursor protein) have not been reported in CSF of patients with ALS so far. In contrast, several other
proteins (transferrin, alpha-1-antitrypsin precursor and beta-2-microglobulin) seem to be unspecifically affected in different
neurological diseases and may therefore be of limited value as disease-related biochemical markers in ALS. Further evaluation
of the candidate proteins identified here is necessary. 相似文献
119.
Zeng LF Zhang HS Wang YH Sanchez T Zheng YT Neamati N Long YQ 《Bioorganic & medicinal chemistry letters》2008,18(16):4521-4524
Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1 integrase (IN) inhibitors. The synthesis of the heteroaromatic carboxylic acids was established by employing phenyl beta-diketoester or benzaldehyde as the starting material and 1,3-dipolar cycloaddition as the key reaction. Of the compounds tested, the 3-benzyloxyphenyl-substituted isoxazole carboxylic acid displayed the best IN inhibitory and antiviral activities, with N-hydroxylamidation enhancing the in vitro and in vivo potency. These findings are important for further optimization of ADK-based IN inhibitors. 相似文献
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Hernández AS Swartz SG Slusarchyk D Yan M Seethala RK Sleph P Grover G Dickinson K Giupponi L Harper TW Humphreys WG Longhi DA Flynn N Murphy BJ Gordon DA Biller SA Robl JA Tino JA 《Bioorganic & medicinal chemistry letters》2008,18(6):2067-2072
1H-tetrazole-1-alkanenitrile SR-9g exhibits a >10-fold in vivo potency enhancement over the lead nitrile 1 and has acceptable oral bioavailability in rats and dogs. An enantiospecific synthesis of 1H-tetrazole-1-alkanenitrile nitriles 9 has been developed. 相似文献